The presence of islet-directed auto-immunity and associated circulating auto-antibodies, previously thought to be primarily characteristic of type-1 diabetes mellitus (T1DM), is now apparent in a proportion of individuals with putative type-2 diabetes (T2DM), consistent with an increasing appreciation of diabetes as a continuous spectrum. Based on the observations that: 1) >98 percent of new-onset cases of T1DM have one or more auto-antibodies; 2) the number of auto-antibodies is proportional to risk of developing T1DM, with any one corresponding to an almost 30-fold increase in risk; 3) the presence of auto-antibodies in adolescents with apparent T2DM defines a distinct patient group that may require different treatment regimens; and 4) the presence of auto-antibodies in adults with presumed T2DM can indicate a more rapid progression to insulin dependency, increased screening for autoantibody status in diabetic and pre-diabetic populations is warranted. The major hurdle for reaching the large at-risk population is the lack of a simple-to-use, point-of-car device to rapidly screen for diabetes autoimmune status. The extension of accurate autoantibody detection to alternative body fluids can facilitate the accessibility of this importan diagnostic parameter to at-risk patient groups for more cost-effective and efficient disease detection and monitoring. Our preliminary data support the hypothesis that diabetes auto-antibodies can be reliably assessed in saliva and that their detection is amenable to simple point- of-care, device-based technologies. To demonstrate the utility of this approach, we will pursue the following two Specific Aims in this phase-I application. Specific aim 1: Correlation of autoantibody status in matched serum and saliva samples in classical T1DM and in T2DM. Specific aim 2: Development of a non-invasive, saliva-based, lateral-flow device for detection of autoimmune diabetes. The proposed research, by developing new methods and technologies able to identify individuals at risk of developing type-1 diabetes with a specific focus on point-f-care assays, low-cost/portable devices, non-invasive testing, and assessment of immune status, is directly relevant to the goals of RFA-DK-11-024 and many of the relevant topics described therein.